Experiments are designed to evaluate theories concerning the functional significance of cerebrospinal fluid (CSF). Two experimental approaches are proposed. 1. The major difficulty in assessing the hypothesis that CSF functions as an excretory system for brain has been to determine the characteristics of material transport from brain to CSF. Proposed experiments are designed to investigate this problem by following the time course and route of removal from rat brain of test substances injected into identified intracerebral sites via chronically implanted cannulae. Correlations between diffusion coefficients of injected compounds and rates of removal from brain may indicate the relative importance of diffusion and bulk flow as mechanisms for transporting substances from brain to CSF. Diffusion and bulk flow may also be distinguished by examining the distribution of dye molecules within brain at various times after intracerebral injection. Mathematical models predicting rates of removal from brain and patterns of intracerebral distribution will be developed. Control experiments will assess the effects of cannula implantation on the results. 2. Primitive characteristics of CSF and brain-barrier mechanisms in nurse shark, dogfish and hagfish recommend these species as experimental models for studying the functional significance of CSF. Proposed experiments aim to further characterize relevant anatomical and physiological aspects of CSF and brain-barrier mechanisms. Experimental techniques include electrolyte analysis of plasma and CSF, kinetic analysis of material exchange between plasma and central nervous system, evaluation of concentration profiles in brain of test compounds diffusing from CSF into surrounding nervous tissue, and light and electron microscopy.